DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on April 17, 2026 is acknowledged.
The Office acknowledges the election. However, the Office does not agree with claims that read on the elected invention. For example, claim 69 is directed to an embodiment that is directed to VDJ rearrangements (i.e., Group II); and claim 50 is directed to embodiments directed to VDJ rearrangements or the exon-exon boundary embodiment (i.e., Group III) that requires blocking oligonucleotides. These claims are therefore also withdrawn from further consideration.
In sum, claims 6, 12, 20, 47, 50, and 69 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on April 17, 2026.
Information Disclosure Statement
The IDS received on March 28, 2024 and April 22, 2026 are proper and are being considered by the Examiner.
The IDS dated March 28, 2024 cites US Patent Publication 2008/0144841. However, this patent is titled, “Earhealth Monitoring System and Method III”, having nothing to do with the presently claimed subject matter. While the reference has been considered, Applicants are advised that the citation may have occurred through a typographical error.
Drawings
The drawings received on August 10, 2023 are acceptable.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 3, 9, 29, 31, 42, 63, 66, 68, 83, 86, 97, 100, and 122 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 is indefinite for reciting the phrase, “contacting DNA with a plurality of primers, wherein the plurality of primers comprises at least two primers that anneal to in a parallel orientation to a target region” because it is unclear whether the two primers anneal to the same strand of the DNA (because DNA embraces that which is double stranded) or the two primers anneal to each strand of a DNA double-stranded region that is a “target”. The term “parallel orientation” is achieved in either of the interpretation and therefore, the claim is indefinite. For the purpose of prosecution, the Office adopts the former interpretation as suggested by Figure 1A.
Claim 3 is also indefinite for the same reason.
Claim 1 is also indefinite because it is unclear whether a “downstream” primer is part of the plurality of primers that anneal to the “same strand1” of a target region, or a different primer. For the purpose of prosecution, the downstream primer is construed to mean those of the plurality of primers that annealed downstream from the other primers of the plurality (as implied in Fig. 1A).
Claim 3 is also indefinite for the same reasons.
Claim 31 recites the trademarked reagent, “Q5 High Fidelity DNA polymerase”. The usage of a trademark in a claim is indefinite because the trademark identifies the source of the good and not the good itself. For example, Coke® has maintained its tradename for decades while changing its underlying formula.
Claim 86 recites the limitation, “one or more of a conversion step”, but fails to recite that the conversion is of. While broadness of a claim limitation is not per se indefinite, over-broadness of a limitation is deemed properly indefinite as it is unclear just exactly what part of the method steps is involved in the “conversion”. For the purpose of prosecution, the Office has construed to reasonably apply the limitation to the conversion of sequences on the DNA of the sample.
Claim 86 is also indefinite because the claim recites the steps a proper context of the parent claim 1. Parent claim 1 recites, inter alia, the steps of (A) contacting the DNA of a sample with a plurality of primers; (B) contacting the resulting product with a DNA polymerase, and (C) detection of the presence/absence of a DNA molecule that comprises a structural variation based on sequencing the DNA. Claim 86 recites that the first two steps are performed in a first aliquot, wherein a capture step is performed. The capture is recited as having a sequence-variable target region. Because claim 1 results in the identification of whether a sequence-variable target region is present or not, it is unclear how capture of the sequence-variable target region can be made in steps (A) and (B) before the identification step of (C).
Claim 97 recites the limitation, “such as a second aliquot.” A limitation followed by the words, “such as” is indefinite because it is unclear whether this limitation is actively required or has any weight in further limiting the claim.
Claim 97 is also indefinite because the claim further limits the modified nucleobase as being modified cytosine (see step (b)), but then reverts to referring to “modified nucleobase” in the phrase, “modified nucleobase recognized by the agent is a modified cytosine or a product of a procedure that affects the first nucleobase in the DNA differently from the second nucleobase in the DNA of the sample,” thereby combining a narrow limitation followed by a broad limitation.
Claim 100 is indefinite because a protein cannot be all of the proteins recited in step (b) (due to the usage of “and/or”).
Claim 122 recites that the detecting results in the determination that the subject has cancer. Initially there is no antecedent basis for the term, “subject.” Second, the claim does not provide any context in which cancer can be detected as the parent claim (1) only results in the sequencing of a structural variation.
Claims 9, 29, 31, 42, 63, 66, 68, 83, 86, 97, 100, and 122 are also indefinite by way of their dependency on claim 1.
Conclusion
The Office notes that the withdrawn claims directed to inventions identified as Groups II and III have not yet been rejoined. The reason for the non-rejoinder is due to the withdrawn claims not being properly embraced by the generic claims. Invention covered by Group I (i.e., elected invention) employs a plurality of primers which anneal to the same strand of a target nucleic acid, wherein the extension of the primers is prevented from being extended by an upstream primer of its kind when annealed to a wildtype region (see Fig. 1A) and the prevention of this extension requires that the DNA polymerase have no 5’ to 3’ exonuclease activity and no strand displacement activity. Claims directed to the embodiments directed to VDJ rearrangements (i.e., Group II) do not operate this way as the prevention of the extension is effected not the primers of its kind, but blocking oligonucleotides (see Fig. 4). Similarly, the claims directed to embodiment of Fig. 1C explicitly require the use of a DNA polymerase comprising an exonuclease activity.
Upon clarification how these claims actually are properly embraced by the independent claims 1 and 3, the Office will consider their rejoinder.
Claims are free of prior art.
The closest prior art is Klass et al. (WO 2021/198401 A1, published October 2021). Klass et al. teach a method that employs a plurality of primers that anneal to the same strand of a target nucleic acid (see below FIG. 1):
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As seen, a plurality of primers anneal to the target region of a DNA and the primers are extended by a DNA polymerase (see also “primers … capable of being extended towards …”, section [0050]). When the two regions (see above) are close in proximity due to a breakpoint mutation, the two sets of primers (plurality of forwards and reverse primers) are become close in proximity and exponential amplification occurs. Because amplification must occur by extension of the primers on their 3’ ends, the DNA polymerase must have a strand displacement activity or else the extension would not occur and amplification not occur, rendering the invention of Klass et al. inoperable if utilizing a DNA polymerase without strand displacement activity.
Inquiries
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Young J. Kim whose telephone number is (571) 272-0785. The Examiner can best be reached from 7:30 a.m. to 4:00 p.m (M-F). The Examiner can also be reached via e-mail to Young.Kim@uspto.gov. However, the office cannot guarantee security through the e-mail system nor should official papers be transmitted through this route.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Gary Benzion, can be reached at (571) 272-0782.
Papers related to this application may be submitted to Art Unit 1681 by facsimile transmission. The faxing of such papers must conform with the notice published in the Official Gazette, 1156 OG 61 (November 16, 1993) and 1157 OG 94 (December 28, 1993) (see 37 CFR 1.6(d)). NOTE: If applicant does submit a paper by FAX, the original copy should be retained by applicant or applicant’s representative. NO DUPLICATE COPIES SHOULD BE SUBMITTED, so as to avoid the processing of duplicate papers in the Office. All official documents must be sent to the Official Tech Center Fax number: (571) 273-8300. Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (571) 272-1600.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/YOUNG J KIM/Primary Examiner
Art Unit 1637 June 11, 2026
/YJK/
1 See above interpretation adopted.
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